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Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis.

Alg, VS; Ke, X; Grieve, J; Bonner, S; Walsh, DC; Bulters, D; Kitchen, N; ... Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, .; + view all (2018) Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis. British Journal of Neurosurgery , 32 (3) pp. 255-259. 10.1080/02688697.2018.1427213. Green open access

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Abstract

INTRODUCTION: Abnormalities in Matrix Metalloproteinase (MMP) genes, which are important in extracellular matrix (ECM) maintenance and therefore arterial wall integrity are a plausible underlying mechanism of intracranial aneurysm (IA) formation, growth and subsequent rupture. We investigated whether the rs243865 C > T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences gene transcription) is associated with IA compared to matched controls. MATERIALS AND METHODS: We conducted a case-control genetic association study, adjusted for known IA risk factors (smoking and hypertension), in a UK Caucasian population of 1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to determine the association of the rs243865 C > T functional MMP-2 gene SNP with IA (overall, and classified as ruptured and unruptured). We also undertook a meta-analysis of two previous studies examining this SNP. RESULTS: The rs243865 T allele was associated with IA presence in univariate (OR 1.18 [95% CI 1.04-1.33], p = .01) and in multi-variable analyses adjusted for smoking and hypertension status (OR 1.16 [95% CI 1.01-1.35], p = .042). Subgroup analysis demonstrated an association of the rs243865 SNP with ruptured IA (OR 1.18 [95% CI 1.03-1.34] p = .017), but, not unruptured IA (OR 1.17 [95% CI 0.97-1.42], p = .11). CONCLUSIONS: Our study demonstrated an association between the functional MMP-2 rs243865 variant and IAs. Our findings suggest a genetic role for altered extracellular matrix integrity in the pathogenesis of IA development and rupture.

Type: Article
Title: Association of functional MMP-2 gene variant with intracranial aneurysms: case-control genetic association study and meta-analysis.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1080/02688697.2018.1427213
Publisher version: https://doi.org/10.1080/02688697.2018.1427213
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Extracellular matrix, MMP-2, genetics, intracranial aneurysms, meta-analysis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10044519
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